Microfluidics as an emerging paradigm for assisted reproductive technology: A sperm separation perspective.

Millions of people are subject to infertility worldwide and one in every six people, regardless of gender, experiences infertility at some period in their life, according to the World Health Organization. Assisted reproductive technologies are defined as a set of procedures that can address the infertility issue among couples, culminating in the alleviation of the condition. However, the costly conventional procedures of assisted reproduction and the inherent vagaries of the processes involved represent a setback for its successful implementation. Microfluidics, an emerging tool for processing low-volume samples, have recently started to play a role in infertility diagnosis and treatment. Given its host of benefits, including manipulating cells at the microscale, repeatability, automation, and superior biocompatibility, microfluidics have been adopted for various procedures in assisted reproduction, ranging from sperm sorting and analysis to more advanced processes such as IVF-on-a-chip. In this review, we try to adopt a more holistic approach and cover different uses of microfluidics for a variety of applications, specifically aimed at sperm separation and analysis. We present various sperm separation microfluidic techniques, categorized as natural and non-natural methods. A few of the recent developments in on-chip fertilization are also discussed.

Microfluidic preparation of spermatozoa for ICSI produces similar embryo quality to density-gradient centrifugation: a pragmatic, randomized controlled trial.

STUDY QUESTION: Does processing of spermatozoa for IVF with ICSI by a microfluidic sperm separation device improve embryo quality compared with density-gradient centrifugation? SUMMARY ANSWER: Patients randomized to microfluidic sperm preparation had similar cleavage- and blastocyst-stage embryo quality and clinical and ongoing pregnancy rates to those who underwent standard sperm processing for IVF with ICSI. WHAT IS KNOWN ALREADY: Microfluidic sperm preparation can isolate spermatozoa for clinical use with minimal DNA fragmentation but with unclear impact on clinical outcomes. STUDY DESIGN, SIZE, DURATION: A prospective randomized controlled trial of 386 patients planning IVF from June 2017 through September 2021 was carried out. PARTICIPANTS/MATERIALS, SETTING, METHODS: One hundred and ninety-two patients were allocated to sperm processing with a microfluidic sperm separation device for ICSI, while 194 patients were allocated to clinical standard density-gradient centrifugation (control) at an academic medical centre. MAIN RESULTS AND THE ROLE OF CHANCE: In an intention to treat analysis, there were no differences in high-quality cleavage-stage embryo fraction [66.0 (25.8)% control versus 68.0 (30.3) microfluidic sperm preparation, P = 0.541, absolute difference -2.0, 95% CI (-8.5, 4.5)], or high-quality blastocyst fraction [37.4 (25.4) control versus 37.4 (26.2) microfluidic sperm preparation, P = 0.985, absolute difference -0.6 95% CI (-6, 5.9)] between groups. There were no differences in the clinical pregnancy or ongoing pregnancy rates between groups. LIMITATIONS, REASONS FOR CAUTION: The population studied was inclusive and did not attempt to isolate male factor infertility cases or patients with a history of elevated sperm DNA fragmentation. WIDER IMPLICATIONS OF THE FINDINGS: Microfluidic sperm separation performs similarly to density-gradient centrifugation in sperm preparation for IVF in an unselected population. STUDY FUNDING/COMPETING INTEREST(S): No external funding to declare. M.P.R. is a member of the Clinical Advisory Board for ZyMot® Fertility, Inc. TRIAL REGISTRATION NUMBER: NCT03085433. TRIAL REGISTRATION DATE: 21 March 2017. DATE OF FIRST PATIENT'S ENROLLMENT: 16 June 2017.

Forbidden medically assisted sex selection in Sunni Muslims: a qualitative study.

RESEARCH QUESTION: Son preference is a phenomenon typically prevalent in traditional societies in the Middle East and in East and South Asia. Hence, various sex-selection practices, either natural or medically assisted, have emerged. Islamic law forbids medically assisted sex selection for social reasons. Our aim was to examine the narratives of Sunni Muslim couples who underwent sex selection treatment by using sperm sorting and to understand their reasons for doing so. DESIGN: A qualitative phenomenological study involving in-depth, face-to-face interviews with 31 women who gave birth to a male baby after undergoing sperm-sorting treatment, preimplantation genetic testing sex selection, or both, in a private clinic. RESULTS: Interviewees spoke about the ethical dilemma they faced in choosing to violate the religious prohibition against sex selection; they explained the reasons why they opted to undergo sperm-sorting treatment and why the utmost secrecy surrounded it. CONCLUSIONS: Some Sunni Muslim couples privately defy the Sunni Muslim orthodoxy on their way to becoming parents to male offspring. Sons are preferred over daughters because of the traditional value attached to male offspring in Muslim culture. Therefore, couples who have only daughters may face an ethical dilemma of whether to obey the religious prohibition against sex selection or to violate it and enjoy societal acceptance and recognition for having a son.

High-resolution melt analysis does not reveal mutagenic risk in sexed sperm and in vitro-derived bovine embryos.

The objectives of the present work were to verify whether simultaneous exposure to Hoechst 33342 and UV irradiation during sorting by flow cytometry may induce gene point mutations in bovine sperm and to assess whether the dye incorporated in the sperm may imply a mutagenic effect during the embryonic development. To this aim, high-resolution melt analysis (HRMA) was used to discriminate variations of single nucleotides in sexed vs. non-sexed control samples. Three batches of sorted and non-sorted commercial semen of seven bulls (42 samples) were subjected to HRMA. A set of 139 genes located on all the chromosomes was selected, and 407 regions of the genome covering a total of 83 907 bases were analyzed. Thereafter, sperm of one sexed and one non-sexed batch of each bull was used in in vitro fertilization, and the derived embryos were analyzed (n = 560). One hundred and thirty-three regions of the bovine genome, located in 40 genes, were screened for a total coverage of 23 397 bases. The comparison between the frequencies of variations, with respect to the sequences deposited, observed in the sexed and non-sexed sperm (843 vs. 770) and embryos (246 vs. 212) showed no significant differences (P > 0.05), as measured by chi-square tests. It can be concluded that staining with Hoechst 33342 and exposure to UV during sorting does not lead to significant changes in the frequencies of variants in the commercial sexed semen and in embryos produced in vitro with the same treated sperm.

Sperm Preparation with Microfluidic Sperm Sorting Chip May Improve Intracytoplasmic Sperm Injection Outcomes Compared to Density Gradient Centrifugation.

Does sperm preparation using the FERTILE PLUS™ Sperm Sorting Chip improve fertilization rates, blastocyst formation, utilization, and euploidy rates in patients undergoing intracytoplasmic sperm injection (ICSI), compared with density gradient centrifugation (DGC)? A single-cohort, retrospective data review including data from 53 couples who underwent ICSI cycles within a 12-month period. For each couple, the two closest, consecutive cycles were identified, where one used the standard technique of sperm preparation (DGC) and the subsequent used FERTILE PLUS™, therefore, couples acted as their own controls. Paired samples t-test was used to compare means for the outcomes (fertilization, blastocyst formation, utilization, and euploidy rates). Binary logistic regression analysis assessed the relationship between female age, the presence of male factor infertility, and euploidy rates. Blastocyst, utilization, and euploidy rates were significantly higher for cycles using FERTILE PLUS™ compared to DGC (76% vs 56%, p = 0.002; 60% vs 41%, p = 0.005, and 40% vs 20%, p = 0.001, respectively). Although there was an increase in fertilization rates for cycles using FERTILE PLUS™, this was not significant (72% vs 68%, p = 0.449). The euploidy rates of females ≤ 35 years were significantly increased when the FERTILE PLUS™ sperm preparation method was used, compared to the older age group (OR 2.31, p = 0.007). No significant association was found between the presence or absence of male factor infertility and euploidy rates between the two cycles. This study provides tentative evidence that the FERTILE PLUS™ microfluidic sorting device for sperm selection can improve blastocyst formation, utilization, and euploidy rates following ICSI in comparison to the DGC method.

Enhancing Intracytoplasmic Sperm Injection Outcomes With Zeta Sperm Selection: A Case Report.

Sperm morphology significantly influences the fertilization capacity of male germ cells. Morphological abnormalities are frequently associated with an overproduction of reactive oxygen species (ROS), leading to further sperm damage and subsequent infertility. This case study examines a couple facing infertility, with male factor infertility identified as the primary issue, characterized by teratozoospermia and a high DNA fragmentation index (DFI). The objective was to assess the efficacy of zeta potential (ZP) as a sperm sorting technique for intracytoplasmic sperm injection (ICSI) in patients showing high DNA fragmentation. A 34-year-old male with abnormal sperm parameters underwent ICSI using the ZP technique for sperm separation, while his 28-year-old female partner received ovarian stimulation. This intervention resulted in the development of two good-quality blastocysts, resulting in a successful embryo transfer (ET) and a positive pregnancy outcome. Previous attempts using conventional assisted reproductive technologies (ART), including in vitro fertilization (IVF), followed by ICSI and ET, as well as other sperm selection methods, were not successful. The ZP-based approach demonstrated significant benefits by selecting spermatozoa with optimal parameters, such as negative membrane potential, thereby enhancing the success rate. This case emphasizes the advantages of personalized treatment strategies in managing male infertility and highlights the potential of advanced sperm sorting techniques in improving fertility outcomes.

Exhaustion of racing sperm in nature-mimicking microfluidic channels during sorting.

Fertilization is central to the survival and propagation of a species, however, the precise mechanisms that regulate the sperm's journey to the egg are not well understood. In nature, the sperm has to swim through the cervical mucus, akin to a microfluidic channel. Inspired by this, a simple, cost-effective microfluidic channel is designed on the same scale. The experimental results are supported by a computational model incorporating the exhaustion time of sperm.

ESHRE Task Force on ethics and Law 20: sex selection for non-medical reasons.

This Task Force document revisits the debate about the ethics of sex selection for non-medical reasons in the light of relevant new technological developments. First, as a result of improvement of the Microsort® flow cytometry method, there is now a proven technique for preconception sex selection that can be combined both with IVF and IUI. Secondly, the scenario where new approaches that are currently being developed for preimplantation genetic screening (PGS) may lead to such screening becoming a routine part of all IVF treatment. In that scenario professionals will more often be confronted with parental requests for transfer of an embryo of a specific sex. Thirdly, the recent development of non-invasive prenatal testing based on cell-free fetal DNA in maternal plasma allows for easy and safe sex determination in the early stages of pregnancy. While stressing the new urgency that these developments give to the debate, the Task Force did not come to a unanimous position with regard to the acceptability of sex selection for non-medical reasons in the context of assisted reproduction. Whereas some think maintaining the current ban is the best approach, others are in favour of allowing sex selection for non-medical reasons under conditions that take account of societal concerns about the possible impact of the practice. By presenting these positions, the document reflects the different views about this issue that also exist in the field. Specific recommendations include the need for a wider delineation of accepted 'medical reasons' than in terms of avoiding a serious sex-linked disorder, and for a clarification of the legal position with regard to answering parental requests for 'additional sex selection' in the context of medically indicated preimplantation genetic diagnosis, or routine PGS.

Microfluidic sperm sorting improves ICSI outcomes in patients with increased values of Double-Strand Breaks in sperm DNA.

BACKGROUND: Delays in embryo kinetics, implantation failures in ICSI treatments and recurrent miscarriages have been associated with high values of Double-Strand Breaks (DSB) in sperm DNA. While conventional methods for semen preparation have been shown to be inefficient reducing DSB values, Microfluidic Sperm Sorting (MSS) devices are promising tools to reduce this damage. OBJECTIVE: To study the clinical utility of an MSS device in ICSI treatments when the male partner presents increased DSB values, as compared to the use of conventional methods based on sperm motility. METHODS: This retrospective cohort study included 28 infertile couples undergoing ICSI treatments. Only couples where the male partner presented increased values of DSB were included. DSB values were evaluated in semen samples by the Neutral Comet assay. Couples performed a first ICSI cycle using conventional methods for semen preparation (Density Gradients and Swim-up) and a second ICSI cycle using the ZyMot™ICSI (formerly named FertileChip®) microfluidic device. Embryology and clinical outcomes were compared between ICSI cycles. RESULTS: Semen parameters and the number of obtained and fertilized oocytes did not show differences between ICSI rounds. Clinical outcomes were statistically better when MSS was used: the biochemical pregnancy rate increased 28.31%; the clinical pregnancy rate increased 35.56% and the number of live births increased 35.29%, as compared to the first ICSI cycle in this group of patients. CONCLUSIONS: The ZyMot™ICSI microfluidic device improved the reproductive outcomes in couples where the male partner presented increased DSB values, when compared to the use of conventional semen preparation techniques.

Separation of motile human sperms in a T-shaped sealed microchannel.

Microfluidic methods act as an effective motile sperm separation technique used in infertility treatments. This work presents a standalone microfluidic device to separate motile sperm cells from non-motile sperm cells and debris. The separation mechanism is based on the centrifugal force acting on sperms and the ability of progressive motile sperms to swim upstream. The separation of motile sperm is carried out using a simple T-shaped microchannel which constitutes three reservoirs: one inlet and two outlets. Herein, one of the outlets is kept sealed. The sealed channel leads to a high-velocity gradient and a rheotaxis zone at the T junction resulting in the separation of motile sperms. Separated sperms are isolated in a sealed channel with a low Reynolds number flow so that sperms cannot have a net displacement, which ensures that the sperms do not re-enter the fluid flow. CFD simulation is conducted to study the flow fields inside the channel and experimental investigation is carried to observe the separation behaviour of sperms. The reported device provides 100% sperm separation efficiency and ensures the entrapment of sperm cells for a longer period. A modified colorimetric nitroblue tetrazolium test conducted on separated sperm cells shows that there is only a marginal increase in superoxide (O2 -) production, proving normal sperm integrity. This device offers an effective and safe alternative to conventional sperm sorting methods. Supplementary Information: The online version contains supplementary material available at 10.1007/s13534-022-00229-9.

A Review of the Impact of Microfluidics Technology on Sperm Selection Technique.

Sperm sorting procedures depend on centrifugation processes. These processes produce oxidative stress and cell damage that are undesirable for in-vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) outcomes because they affect fertilization and implantation chances. The microfluidic sperm selection technique has shown promise in this area. It can create a platform for isolating and manipulating good-quality sperm cells using diverse triggers such as mechanical factors, chemical agents, and temperature gradients. Furthermore, microfluidic platforms can direct sperm cells for IVF or sperm sorting by utilizing an approach that is passive or active. In this review, we explain the use of microfluidics technologies for sorting and arranging sperm cells for different purposes. We also discuss the use of microfluidics technology in selecting and assessing sperm parameters and how it affects male infertility.

Does Microfluidic Sperm Sorting Affect Embryo Euploidy Rates in Couples with High Sperm DNA Fragmentation?

Male infertility contributes as the main factor in 30-50% of infertility cases. Conventional methods for sperm preparation have induced questioning of sperm recovery rates. The microfluidic sperm sorting (MSS) technique selects highly motile sperm with lower levels of SDF (sperm DNA fragmentation) compared to conventional sperm sorting techniques. This study aimed to determine whether utilizing this technique will reveal better embryo quality and euploidy rates in couples with repeated implantation failure (RIF) and high SDF in a new PGT-A (preimplantation genetic testing for aneuploidies) cycle. This retrospective study included couples referred to PGT-A for previous repeated ART (assisted reproductive techniques) cycle failures and with high SDF. In their new cycles, couples who accepted the technique were assigned to the MSS group, and the rest were managed with DGC (density-gradient centrifugation). Two groups were compared in terms of fertilization and euploidy rates, clinical miscarriage and live birth rates, the total number of blastocysts, and top quality blastocysts. There was no difference between the groups regarding fertilization rates, euploidy rates, clinical miscarriage, and live birth rates. The total number of blastocysts and top quality blastocysts were significantly higher in the MSS group. The MSS technique provides a higher number of top-quality blastocysts than DGC; however, neither euploidy nor live birth rates improved. Studies focusing on confounding factors to embryonic genomic status in the presence of high SDF are needed.

In vitro survival kinetics of microfluidic-sorted bovine spermatozoa.

BACKGROUND: The isolation and characterization of sperm subpopulations that can achieve fertilization is a major challenge of assisted reproduction methods. We focused on the microfluidic sperm sorter as a novel tool for collecting highly motile spermatozoa from heterogeneous semen samples. OBJECTIVES: This study primarily aims to obtain baseline information on sorted spermatozoa according to its characteristics and in vitro life span. MATERIALS AND METHODS: Frozen-thawed bull semen was subjected to microfluidic sperm sorting using diffuser-type microfluidic sperm sorter (DMSS). After sorting, samples were collected as the sorted spermatozoa and unsorted residual spermatozoa and incubated at 37°C for subsequent evaluation. The samples were assessed at different time points (0 or 1, 6, and 24 h) in terms of motility, which was measured by computer-assisted sperm analysis (CASA), membrane integrity, mitochondrial function, and adenosine triphosphate (ATP) production after sorting (0 h). To determine the characteristics and efficiency of DMSS sorting, the sorted spermatozoa were compared with samples collected using the swim-up method, a conventional method in motile sperm selection. RESULTS: A comparison between the sorted and residual spermatozoa demonstrated significantly higher motility parameters, membrane integrity, and mitochondrial function of the sorted spermatozoa until 6 h after incubation. The time course decrement of membrane and mitochondrial status were subjected to curve fitting and theoretically supported. Sperm ATP production measured immediately after sorting showed higher ATP generation of the sorted spermatozoa compared with the unsorted, frozen-thawed spermatozoa. The motility parameters and mitochondrial activity of DMSS-sorted spermatozoa were higher than the swim-up-collected spermatozoa (p < 0.05). DISCUSSION AND CONCLUSION: These results indicate that DMSS sorting can strictly select highly motile spermatozoa with the ability to maintain its membrane integrity and mitochondrial function related to ATP production. We speculate that the device that is able to sort high-quality spermatozoa can have great potential in assisted reproduction.

Microfluidic sperm selection yields higher sperm quality compared to conventional method in ICSI program: A pilot study.

An appropriate preparation technique, should be capable of isolating highquality spermatozoa for intracytoplasmic sperm injection (ICSI). The aim was to assess sperm quality parameters, DNA integrity, embryo development, and clinical outcomes using a practical and accessible Microfluidic Sperm Sorting (MSS) technique. A total of 95 ICSI cases performed using sperm samples were prepared with our MSS (group 1) or by Direct Swim Up (DSU; control) method (group 2). Both sperm quality parameters and sperm DNA fragmentation (SDF) were compared between the groups. DNA fragmentation was assessed using Sperm Chromatin Dispersion (SCD) test and fine morphology was assessed using Motile Sperm Organelle Morphology Examination (MSOME). Embryo development and clinical outcomes were compared between the groups. In the MSS group, progressive motility and the fraction of Class I sperm morphology sperm were significantly higher compared to DSU group (P < 0.01 and P < 0.001, respectively). Moreover, the rates of DNA fragmentation and immotile spermatozoa were significantly lower in MSS when compared to DSU group (P < 0.001). Also, higher rates of high-quality embryo formation (P < 0.001), implantation (P = 0.04) and pregnancy (P = 0.05) were achieved in the MSS compared to DSU groups. The MSS technique proved to be a noninvasive, disposable, easy to use, and inexpensive method for separation of high-quality spermatozoa. Both laboratory parameters and clinical outcomes were improved with application of MSS for neat sperm collection in ICSI.AbbreviationsICSI: Intracytoplasmic Sperm Injection; MSS: Microfluidic Sperm Sorting; Sperm DNA Fragmentation (SDF); SCD: Sperm Chromatin Dispersion; MSOME: Motile Sperm Organelle Morphology Examination; DGC: Density Gradient Centrifugation; DSU: Direct Swim Up; ROS: Reactive Oxygen Species; ART: Assisted Reproducetive Technology.

Viscous Cervical Environment-on-a-Chip for Selecting High-Quality Sperm from Human Semen.

When ejaculated sperm travels through the vagina to the uterus, mucus secreted by the cervical canal generally filters out sperm having low motility and poor morphology. To investigate this selection principle in vivo, we developed a microfluidic sperm-sorting chip with a viscous medium (polyvinylpyrrolidone: PVP) to imitate the biophysical environment mimic system of the human cervical canal. The material property of the PVP solution was tuned to the range of viscosities of cervical mucus using micro-viscometry. The selection of high-quality human sperm was experimentally evaluated in vitro and theoretically analyzed by the convection-diffusion mechanism. The convection flow is shown to be dominant at low viscosity of the medium used in the sperm-sorting chip when seeded with raw semen; hence, the raw semen containing sperm and debris convectively flow together with suppressed relative dispersions. Also, it was observed that the sperm selected via the chip not only had high motilities but also normal morphologies and high DNA integrity. Therefore, the biomimetic sperm-sorting chip with PVP medium is expected to improve male fertility by enabling the selection of high-quality sperm as well as uncovering pathways and regulatory mechanisms involved in sperm transport through the female reproductive tract for egg fertilization.

Sperm selection in IVF: the long and winding road from bench to bedside.

Spermatozoa wage battle to conquer fertilization but the traits needed to succeed remain elusive. The natural advantageous qualities that enable only a few selected sperm cells to reach the site of fertilization remain unknown. Although in vitro fertilization (IVF) facilitates the job of spermatozoa, a universally acceptable means of sperm selection is yet to be developed. No objective or reliable sperm quality indicators have been established and sperm selection is, to a great extent, based on subjective qualitative evaluation. The best method for sperm selection in IVF presents several challenges: intrinsic sperm qualities cannot be evaluated and the ideal endpoint for these studies is debatable. An ideal method for sperm selection in ART should be noninvasive and cost-effective, and allow the identification of high-quality spermatozoa and yield better outcomes in terms of pregnancy and live birth rates. This narrative review included 85 papers and focused on the new available methods and technologies that might shed some light on sperm selection in IVF. It discusses the available data on microfluidic devices, omics profiling, micronuclei studies, sperm plasma membrane markers, and other techniques, such as Magnetic Activated Cell Sorting (MACS), Raman micro-spectroscopy, and artificial intelligence systems. The new techniques herein reviewed offer fresh approaches to an old problem, for which a definite solution has yet to cross the bridge from bench to IVF clinics around the world, since clinical usefulness and application remain unproven.

Sperm selection in assisted reproduction: A review of established methods and cutting-edge possibilities.

Male infertility often involves idiopathic or unknown causes, leading to an increasing demand for assisted reproduction technologies (ART). Conventional sperm sorting techniques rely on centrifugation steps that are known to cause oxidative stress and consequently damage cells. Alternative novel techniques have been introduced but offer disadvantages that need to be overcome. These techniques are also employed to increase the number and the quality of subjects in the animal breeding industry, to obtain purebred subjects or to preserve endangered animal species. Microfluidics deals with the manipulation of small amounts of volume within a microdevice known as lab-on-a-chip (LOC), which offers rapid analyses, ease of use, small reagent sample volumes, high-throughput processing and wide reproducibility owing to automation and standardization. As the LOC allows gamete handling within a microenvironment that strictly mimics physiological in vivo conditions and avoids centrifugation steps and long processing time, the use of microfluidics for sperm sorting and selection have been proposed during the last 15 years and is currently under investigation. Moreover, LOC technologies to sort, identify and analyse other kinds of cells could be transferred to sperm selection and analysis, thus opening the way to a novel approach to the sperm cell selection and manipulation. This review describes the techniques routinely performed in human and animal clinical practice for sorting good-quality sperm for in vitro fertilization procedures, and focuses on the positive and negative aspects of each method. Emerging microfluidic devices, recently proposed for sperm selection, are also described and, when possible, compared with standard methods.

Review on Sperm Sorting Technologies and Sperm Properties toward New Separation Methods via the Interface of Biochemistry and Material Science.

Successful fertilization in mammals requires spermatozoa to efficiently traverse the female reproductive tract to meet the egg. This process naturally selects high quality sperm cells for fertilization, but when artificial reproductive technologies are used such as in vitro fertilization, intracytoplasmic sperm injection, or intrauterine insemination, other methods of sperm selection are required. Currently, technology enables sperm sorting based on motility, maturity as defined by zeta potential or hyaluronic acid binding site expression, absence of apoptotic factors, appropriate morphology, and even sex. This review summarizes current knowledge on all known methods of sperm cell sorting, compares their efficiency, and discusses the advantages and limitations of each technique. Scope for further refinement and improvement of current methods are discussed as is the potential to utilize a variety of materials to innovate new methods of sperm separation.

Comparison of microfluid sperm sorting chip and density gradient methods for use in intrauterine insemination cycles.

OBJECTIVE: To compare the effect of microfluiding sperm sorting chip and density gradient methods on ongoing pregnancy rates (PRs) of patients undergoing IUI. DESIGN: Retrospective cohort study. SETTING: Hospital IVF unit. PATIENT(S): Couples with infertility undergoing IUI cycles between 2017 and 2018. INTERVENTION(S): Not applicable. MAIN OUTCOME MEASURE(S): Ongoing PRs. RESULT(S): A total of 265 patients were included in the study. Microfluid sperm sorting and density gradient were used to prepare sperm in 133 and 132 patients, respectively. Baseline spermiogram parameters, including volume, concentration, motility, and morphology, were similar between the two groups. Total motile sperm count was lower in the microfluiding sperm sorting group at baseline (35.96 ± 37.69 vs. 70.66 ± 61.65). After sperm preparation sperm motility was higher in the microfluid group (96.34 ± 7.29 vs. 84.42 ± 10.87). Pregnancy rates were 18.04% in the microfluid group and 15.15% in the density gradient group, and ongoing PRs were 15.03% and 9.09%, respectively. After using multivariable logistic regression and controling for confounding factors, there was a significant increase in ongoing PRs in the microfluid sperm sorting group. The adjusted odds ratio for ongoing pregnancy in the microfluid group compared with the density gradient group was 3.49 (95% confidence interval 1.12-10.89). CONCLUSION(S): The microfluid sperm sorting method significantly increased the ongoing PRs compared with the density gradient group in IUI cycles.

Microfluidic-based sperm sorting & analysis for treatment of male infertility.

Microfluidics technology has emerged as an enabling technology for different fields of medicine and life sciences. One such field is male infertility where microfluidic technologies are enabling optimization of sperm sample preparation and analysis. In this chapter we review how microfluidic technology has been used for sperm quantification, sperm quality analysis, and sperm manipulation and isolation with subsequent use of the purified sperm population for treatment of male infertility. As we discuss demonstrations of microfluidic sperm sorting/manipulation/analysis, we highlight systems that have demonstrated feasibility towards clinical adoption or have reached commercialization in the male infertility market. We then review microfluidic-based systems that facilitate non-invasive identification and sorting of viable sperm for in vitro fertilization. Finally, we explore commercialization challenges associated with microfluidic sperm sorting systems and provide suggestions and future directions to best overcome them.